Atherosclerosis Disease Management (eBook)

Dr. Jasjit Suri has spent over 20 years in biomedical engineering/sciences/devices and his last 14 years has been dedicated in the field of medical imaging modalities and its fusion. He has published more than 300 technical papers in body imaging and devices, relating to modalities like MR, CT, X-ray, Ultrasound, PET, SPECT, Elastography and Molecular Imaging. Dr. Chirinjeev Kathuria holds a Bachelor of Science (B.Sc.) degree and specialized in U.S. Health Care Policy and Administration and a Doctor of Medicine (M.D.) from Brown University. He also holds a Master's in Business Administration (M.B.A.) from Stanford University. Dr. Filippo Molinari received the Italian Laurea and the Ph.D. in Electrical Engineering from the Politecnico di Torino, Torino, Italy, in 1997 and 2000, respectively. Since 2002, he has been an assistant professor on the faculty of the Department di Electronics, Politecnico di Torino, where he teaches biomedical signal processing, biomedical image processing, and instrumentation for medical imaging.

Contents 6
Contributors 10
Part I Histology, Pathologies and Associated Risks 16
Chapter 1: Introduction to the Pathology of Carotid Atherosclerosis: Histologic Classification and Imaging Correlation 17
1.1 Introduction 17
1.2 Atherosclerosis: A Historical Perspective 18
1.3 Introduction to Carotid Artery Atherosclerosis 19
1.3.1 Pathologic Evaluation of the Carotid Endarterectomy Specimen 19
1.3.2 Localization of Plaque at the Carotid Bifurcation 20
1.4 Classification of Atherosclerotic Disease 21
1.4.1 The AHA Classification Scheme 21
1.4.2 Limitations of the AHA Classification 22
1.4.3 Pathologic Features of Atherosclerosis and Modifications to the AHA Classification 24
1.4.3.1 Early, Asymptomatic Lesions 24
Intimal Thickening and Intimal Xanthoma 24
Pathological Intimal Thickening 25
1.4.3.2 Advanced Symptomatic Lesions 25
Fibrous Cap Atheroma 25
Progression of Atherosclerosis Leading to Plaque Enlargement 25
Intraplaque Hemorrhage 25
Thin Cap Fibrous Atheroma (Vulnerable Plaque) 26
Lesions with Thrombi 28
Plaque Rupture with Luminal Thrombus/Organizing Thrombus 28
Plaque Rupture with Ulceration 29
Plaque Erosion 29
Calcified Nodule 29
1.4.3.3 Stable Atherosclerotic Plaque 30
Healed Rupture/Erosion 30
Fibrocalcific Plaques 31
Chronic Total Occlusion 31
1.4.4 Carotid vs. Coronary Disease: Differences in Plaque Morphology 31
1.5 Risk Factors Contributing to Symptomatic Carotid Disease and Correlation with Plaque Morphology 32
1.6 Comparison of Carotid Plaque Histology from Symptomatic and Asymptomatic Patients 33
1.7 Imaging Modalities for Carotid Arteries and Histopathological Correlation 36
1.7.1 Digital Subtraction Angiography 36
1.7.2 Doppler Ultrasound 36
1.7.3 CT Angiography 37
1.7.4 Magnetic Resonance Imaging 37
1.7.5 Role of Inflammation in Imaging 39
1.8 Conclusions 41
References 41
Chapter 2: Cardiovascular Risk in Subjects with Carotid Pathologies 50
2.1 Carotid Disease is an Index of Diffuse Atherosclerosis, Including Coronary Heart Disease 51
2.2 Cardiovascular Risk and CHD in Patients with Specific Conditions 52
2.2.1 Asymptomatic CVD 52
2.2.2 Patients with TIA/Stroke 52
2.2.3 Candidates for Carotid Endarterectomy 54
2.3 Controversies About Need for CHD Testing in Patients with CVD and Measures to Be Taken in Case of Positive Testing 56
2.4 Intima–media Thickness of the Carotid Artery and Cardiac Risk 58
2.4.1 Correlation with Coronary Angiography 58
2.4.2 Correlation with Cardiac Events 58
2.5 Conclusions 60
References 60
Chapter 3: Neurological Evaluation and Management of Patients with Atherosclerotic Disease 65
3.1 Stroke as Social Problem 65
3.2 Stroke and Atherosclerosis Early Prevention and Management 66
3.3 Objectives and End Points 68
3.4 Experimental Setup 69
3.4.1 Patients Inclusion Criteria 69
3.4.2 Exclusion Criteria 70
3.4.3 Ethical Issues 70
3.4.4 Functional and Instrumental Clinical Examinations 71
3.4.4.1 Clinical Examination 71
3.4.4.2 Laboratory and Hematochemical Exams 71
3.4.4.3 Instrumental Examinations 71
3.5 Sample Instrumental Data 72
3.6 Results and Impact on the Management of the Patient with Neurological Symptoms 75
References 78
Chapter 4: Pathology of Atherosclerotic Disease 82
4.1 Epidemiology of Atherosclerosis 83
4.2 Risk Factors 83
4.3 Normal Anatomy of the Arterial Vascular Wall 84
4.4 Pathology 85
4.5 Elementary Atheromasic Injuries 85
4.6 Relationship between fibrous capsule and prognostic significance of the lesions 90
4.7 Complicated Atheromasic Injuries 91
4.7.1 Calcification 91
4.7.2 Ulcers and Plaque Rupture 92
4.8 Etiopathogenetic Theories 93
References 94
Chapter 5: Stress Analysis on Carotid Atherosclerotic Plaques by Fluid Structure Interaction 97
5.1 Background 98
5.1.1 Stress-Related Plaque Rupture Hypothesis 98
5.1.2 Stress Studies on Plaques 99
5.1.2.1 2D Versus 3D Structure-Only Stress Analysis 100
5.1.2.2 3D Structure Analysis Only Versus Fluid Structure Interaction Stress Analysis 101
5.2 Methodology 103
5.2.1 Carotid Plaque Reconstructions from In Vivo MRI 103
5.2.1.1 MR Imaging Acquisition 103
5.2.1.2 3D Carotid Bifurcation and Arterial Plaque Reconstruction 103
Plaque Components Segmentation 103
3D Geometry Reconstruction of Carotid Bifurcation 105
5.2.2 FSI Simulation and Boundary Conditions 107
5.3 Simulation Result on Different Applications 109
5.3.1 Stress Analyses with Multiple Patients 109
5.3.1.1 Fluid Domain Results 110
5.3.1.2 Wall Tensile Stress 110
5.3.1.3 Wall Tensile Stress in the Fibrous Cap 112
5.3.1.4 Impact of Plaque Morphology to the Stress Distributions 113
5.3.2 Stress Analysis with TIA Patients 116
5.3.3 Effects of Lipid Core Volume and Fibrous Cap Thickness on Stress Distribution 118
5.4 Modeling Procedure Uncertainties Analysis 120
5.4.1 Geometry Reconstruction Reproducibility 120
5.4.2 Variation of Material Model Definition 121
5.4.3 Axial Stretch 122
5.4.4 Residual Stress 122
5.5 Discussions and Conclusion 123
5.6 Conclusion 124
References 125
Part II Ultrasound Imaging 129
Chapter 6: Methods in Atherosclerotic Plaque Characterization Using Intravascular Ultrasound Images and Backscattered Signals 130
6.1 Introduction 130
6.2 IVUS Data Collection Specification 131
6.2.1 In Vivo Acquisition 131
6.2.2 In Vitro Setup and Specimen Preparation 132
6.2.2.1 Local Marking of ROIs 133
6.2.2.2 Systematic Marking of ROIs 136
6.3 New Intravascular Ultrasound Methods for Atherosclerotic Plaque Characterization 137
6.3.1 Spectral and RF-Based Approaches 137
6.3.1.1 IVUS-Virtual Histology 138
6.3.1.2 IVUS-Integrated Backscatter 138
6.3.1.3 IVUS Elastography 140
6.3.2 Texture-Based Approaches 143
6.3.2.1 IVUS-Prognosis Histology 143
6.3.2.2 IVUS-Error Correcting Output Codes 145
6.3.2.3 IVUS-Image-Based Histology (IVUS-IBH) 147
6.4 Challenges Associated with Atherosclerotic Tissue Characterization Algorithms 149
6.4.1 Variability of Tissue Signatures 150
6.4.2 Consistency Among PH Images in Adjacent Frames 151
6.4.3 Effects of Change of Pressure 151
6.4.4 Effects of Flowing Blood 153
6.4.5 Interpretation of Histological Images, Labeling of IVUS Frames, and Sufficiency of Data Sets 154
6.4.6 Classification of Tissues Behind the Arc of Calcified Plaques 155
6.5 Summary and Conclusion 156
Biographies 160
References 156
Chapter 7: Despeckle Filtering of Ultrasound Images 162
7.1 Introduction 163
7.2 Despeckle Filtering 166
7.2.1 Local Statistics Filtering 167
7.2.1.1 First-Order Statistics Filtering (DsFlsmv, DsFwiener) 167
7.2.1.2 Homogeneous Mask Area Filtering (DsFlsminsc) 168
7.2.2 Median Filtering (DsFmedian) 169
7.2.3 Maximum Homogeneity Over a Pixel Neighborhood Filtering (DsFhomog) 169
7.2.4 Geometric Filtering (DsFgf4d) 169
7.2.5 Homomorphic Filtering (DsFhomo) 170
7.2.6 Diffusion Filtering 171
7.2.6.1 Anisotropic Diffusion Filtering (DsFad) 171
7.2.6.2 Coherent Nonlinear Anisotropic Diffusion Filtering (DsFnldif) 172
7.2.7 Wavelet Filtering (DsFwaveltc) 173
7.3 Methodology 174
7.3.1 Material 174
7.3.2 Recording of Ultrasound Images 174
7.3.3 Despeckle Filtering 174
7.3.4 Texture Analysis 175
7.3.5 Distance Measures 175
7.3.6 Univariate Statistical Analysis 176
7.3.7 kNN Classifier 176
7.3.8 Image Quality Evaluation Metrics 176
7.3.9 Visual Evaluation by Experts 178
7.4 Results 179
7.4.1 Evaluation of Despeckle Filtering on a Symptomatic Ultrasound Image and a Cardiac Image 179
7.4.2 Texture Analysis: Distance Measures, Table 7.2 180
7.4.3 Texture Analysis: Univariate Statistical Analysis, Table 7.3 182
7.4.4 Texture Analysis: kNN Classifier, Table 7.4 182
7.4.5 Image Quality Evaluation Metrics, Table 7.5 187
7.4.6 Visual Evaluation by Experts, Table 7.6 187
7.4.7 Intima–Media Complex and Plaque Segmentation 190
7.5 Discussion 192
7.6 Summary and Future Directions 196
7.6.1 Summary 196
7.6.2 Future Directions 198
Biographies 203
7.8 Appendix: An Example of Running the Despeckle Filtering Toolbox 199
References 199
Chapter 8: Use of Ultrasound Contrast Agents in Plaque Characterization 204
8.1 Introduction 205
8.2 Basics of Plaque Characterization by Ultrasounds 207
8.3 Experimental Protocol and Patients Selection 208
8.4 Ultrasound Images Segmentation Strategy 210
8.5 Plaque Characterization in Contrast: Enhanced Ultrasound Images 212
8.6 ceUS Plaque Characterization and Histology 216
8.6.1 Plaque with Calcium Deposits 216
8.6.2 Soft Unstable Plaque 218
8.7 Discussions, Limitations, and Future Perspectives 220
Biographies 226
References 222
Chapter 9: An Integrated Approach to Computer-Based Automated Tracing and IMT Measurement for Carotid Artery Longitudinal Ultrasound Images 229
9.1 Introduction 230
9.2 CALEXia Architecture 233
9.2.1 Automatic Recognition of the Common Carotid Artery 233
9.2.1.1 Selection of Seed Points 233
9.2.1.2 Fitting of Line Segments and Its Tracing 235
9.2.1.3 Line Segments Recognition and Classification 240
9.2.2 IMT Measurement Strategy 242
9.3 Design of Performance Metric 244
9.3.1 Image Database 244
9.3.2 Polyline Distance Metric and Performance Metric 245
9.3.2.1 Polyline Distance Metric 245
9.3.2.2 Mean System Error 247
9.3.2.3 IMT Metric 247
9.4 Performance Evaluation and Benchmarking 248
9.4.1 Automated Tracings of the Carotid Artery 248
9.4.2 Carotid Wall Segmentation and IMT Measurement 250
9.5 CALEXia Merits, Problems, and Perspectives 252
9.6 Conclusions 256
Biographies 258
References 256
Chapter 10: Inter-Greedy Technique for Fusion of Different Segmentation Strategies Leading to High-Performance Carotid IMT Measurement in Ultrasound Images 260
10.1 Introduction 261
10.2 Architecture of CULEXsa 263
10.3 Architecture of CALEXia 265
10.4 Architecture Based on Morphological Approach of Watershed Transform 266
10.5 Inter-Greedy Approach for Fusion of Multiple Image Processing Boundaries 269
10.6 Performance Evaluation Metrics and Image Dataset 271
10.7 Segmentation Performance 272
10.7.1 Performance Evaluation of Segmentation Techniques for Lumen–Intima 274
10.7.2 Performance Evaluation of Segmentation Techniques for Media–Adventitia 275
10.7.3 Performance of Greedy with Respect to CALEXia, CULEXsa, and WS 277
10.8 Error per Vertex for Different Segmentation Techniques 280
10.9 Intima–Media Thickness Measurement Performance of CALEXia, CULEXsa, WS, and Inter-Greedy Algorithms 281
10.10 Conclusions 282
Biographies 285
References 283
Chapter 11: Techniques and Challenges in Intima–Media Thickness Measurement for Carotid Ultrasound Images: A Review 287
11.1 Introduction 288
11.1.1 Rationale and Applications 288
11.1.2 Clinical Importance of Vessel Wall Segmentation 289
11.1.3 Relationship of Computer Measurements and CVD 292
11.1.4 Monitoring of Carotid Wall Evolution 292
11.2 Challenges in Carotid Wall Segmentation 293
11.2.1 Biological Variability in Normal and Pathology 294
11.2.2 Instrumental Variability 295
11.2.3 Noise Sources 295
11.3 Computer Methods in Carotid Wall Segmentation 297
11.3.1 Edge Tracking and Gradient-Based Techniques 297
11.3.2 Dynamic Programming Techniques 301
11.3.3 Active Contours (Snakes)-Based Segmentation 302
11.3.4 Local Statistics and Snakes 305
11.3.5 Nakagami Modeling 308
11.3.6 Hough Transform 310
11.3.7 Integrated Approach 311
11.3.8 3-D Segmentation Methods 312
11.3.9 IVUS Techniques 313
11.4 A Discussion on Correlation with Human Tracings 315
11.4.1 Mean Absolute Distance 315
11.4.2 Hausdorff Distance 316
11.4.3 Polyline Distance Metric 317
11.4.4 Percent Statistic Test 318
11.4.5 Manual and Computer-Measured IMT 319
11.5 Discussion and Future Perspectives 320
11.6 Conclusions 321
Biographies 329
References 322
Chapter 12: 3D Carotid Ultrasound Imaging 331
12.1 Introduction 332
12.2 3D Carotid Ultrasound Scanning Technique 333
12.2.1 Mechanical Linear 3D Carotid Ultrasound Imaging 333
12.2.2 3D Carotid Ultrasound Image Reconstruction 336
12.2.3 Viewing of 3D Carotid Ultrasound Images 336
12.3 Quantification of Carotid Atherosclerosis 337
12.3.1 Total Plaque Volume 337
12.3.2 Vessel Wall Volume 337
12.4 3D Carotid US Studies 337
12.4.1 Monitoring Carotid Atherosclerosis Regression 337
12.4.1.1 TPA Measurements of Intensive Statin Treatment of Carotid Atherosclerosis 340
12.4.1.2 VWV Measurements of Intensive Statin Treatment of Carotid Atherosclerosis 341
12.4.1.3 Generation of 3D and 2D Carotid Maps 343
12.4.1.4 Mapping Spatial and Temporal Changes in Carotid Atherosclerosis from 3D Images 346
12.5 Discussion 349
References 350
Part III X-Rays, CT, and MR Clinical Imaging 357
Chapter 13: CT Imaging in the Carotid Artery 358
13.1 General Introduction 358
13.2 CT Principles 359
13.2.1 General Overview 359
13.2.2 Scanning Parameters 361
13.3 Basic Post-processing Techniques in CTA 362
13.3.1 CTA Issues 369
13.4 Carotid Artery Imaging 370
13.4.1 Imaging Diagnostic Flowchart 370
13.4.2 Imaging Techniques 371
13.4.3 Digital Subtraction Angiography 371
13.4.4 Ultrasound Echo Colour Doppler 372
13.4.5 Magnetic Resonance Angiography 374
13.4.6 Other Imaging Modalities 376
13.4.6.1 [18F]-Fluorodeoxyglucose Positron Emission Tomography 376
13.4.6.2 Single-Photon Emission Computed Tomography 377
13.4.6.3 Scintigraphy 378
13.5 Carotid Artery Pathology and Stroke Risk 378
13.6 From the Concept of Luminal Narrowing to the Carotid Vulnerable Plaque 382
13.7 Plaque Luminal Morphology 384
13.7.1 Smooth Surface 384
13.7.2 Plaque Irregularities 384
13.7.3 Plaque Ulcerations 384
13.8 Analysis of the Different Types of Plaque 388
13.9 Carotid Plaque Volume 392
13.10 Plaque Components 393
13.10.1 Fibrous Cap 393
13.10.2 Intra-plaque Haemorrhage 396
13.10.3 Plaque Thrombus 396
13.10.4 Plaque Calcification 397
13.11 Plaque Eccentricity and Remodelling 398
13.12 Carotid Plaque Enhancement 399
13.13 Other Imaging Concepts on Carotid 400
13.13.1 The Carotid Artery Wall Thickness 400
13.13.2 Automated Plaque Analysis 401
13.14 Conclusion 402
Biography 414
References 402
Chapter 14: Fast, Accurate Unsupervised Segmentation of 3D Magnetic Resonance Angiography 415
14.1 Introduction 415
14.2 Slice-Wise Segmentation with the LCDG Models 418
14.3 Experimental Results 420
14.3.1 Segmentation of Natural TOF- and PC-MRA Images 421
14.3.2 Validating the Segmentation Accuracy with Special Phantoms 425
14.4 Conclusion 427
Biographies 434
14.5 Appendix: EM-Based Precise LCDG-Approximation of a Probability Distribution 428
14.5.1 Sequential EM-Based Initialization 428
14.5.2 Modified EM Algorithm for Refining LCDGs 429
References 431
Chapter 15: Noninvasive Imaging for Risk Prediction in Carotid Atherosclerotic Disease 437
15.1 Introduction 437
15.2 Carotid Plaque 438
15.3 B-Mode Ultrasound 438
15.4 Intima–Media Thickness 439
15.5 Degree of Stenosis 441
15.6 Origin of Stroke 443
15.7 Morphology and Texture of Plaques 444
15.7.1 Histology 444
15.7.2 Stages of Atherosclerosis 444
15.7.3 “Stable Plaque” 446
15.8 High-Resolution Magnetic Resonance Imaging 447
15.8.1 Fibrous Cap Status and Lipid Core 448
15.8.2 Hemorrhage 451
15.8.3 Perspective 454
15.8.4 Limitations of MRI-Based Plaque Imaging 455
Biographies 458
References 455
Chapter 16: Noninvasive Targeting of Vulnerable Carotid Plaques for Therapeutic Interventions 461
16.1 Introduction 461
16.2 The Vulnerable Plaque 462
16.3 B-Mode Ultrasonography 464
16.3.1 Intima/Media Thickness 464
16.3.2 Plaque Echogenicity 465
16.3.3 Plaque Irregularity 466
16.3.4 Molecular Contrast-Enhanced Ultrasonography 466
16.4 Magnetic Resonance Imaging 467
16.4.1 Morphological Parameters 468
16.4.1.1 Fibrous Cap and Lipid Rich-Necrotic Core 468
16.4.1.2 Fibrous Cap Disruption and Platelet Aggregation 469
16.4.1.3 Severity of Stenosis 470
16.4.1.4 Intraplaque Hemorrhage 470
16.4.1.5 Expansive Remodeling 471
16.4.1.6 Superficial Calcified Nodules 472
16.4.2 Flow Modeling with Shear Stress Estimation 473
16.4.3 Active Inflammation 475
16.4.3.1 Dynamic Contrast-Enhanced MRI and Neovascularization 476
16.4.3.2 USPIO-Enhanced MRI and Macrophage Content 477
16.5 Positron Emission Tomography and Single Photon Emission Computed Tomography 479
16.5.1 Inflammation 480
16.6 The Vulnerable Plaque in Clinical Trials 481
16.7 Future Directions 485
16.8 Summary 487
Biographies 497
References 490
Chapter 17: Noninvasive Imaging of Carotid Atherosclerosis 500
17.1 Introduction 500
17.2 Ultrasonography 502
17.2.1 Conventional B-Mode US 502
17.2.2 Contrast-Enhanced US 505
17.3 Transcranial Doppler 505
17.4 Multidetector-Row Computed Tomography 507
17.5 Magnetic Resonance Imaging 508
17.5.1 Conventional MRI 509
17.5.2 Dynamic CE MRI 512
17.5.3 Ultrasmall Particles of Iron Oxide-Enhanced MRI 513
17.6 Nuclear Imaging Techniques 514
17.6.1 Fluorine-18-Fluorodeoxyglucose PET 515
17.6.2 Annexin A5 Scintigraphy 516
17.7 Summary and Future Research Directions 517
Biographies 525
References 519
Part IV Treatment and Monitoring ofAtherosclerosis 529
Chapter 18: Treatment of Carotid Stenosis: Carotid Endarterectomy and Carotid Angioplasty and Stenting 530
18.1 Introduction 530
18.1.1 Diagnostic Tests 531
18.1.1.1 Duplex Scan 531
18.1.1.2 Magnetic Resonance Imaging 533
18.1.1.3 Computed Tomography Angiography 534
18.1.1.4 Angiography 534
18.1.2 Symptomatic and Asymptomatic Carotid Stenosis 535
18.1.3 Anaesthesiological Technique 536
18.1.4 Surgical Technique 540
18.1.4.1 Standard CEA (Direct Suture or with Patch) 541
18.1.4.2 Eversion Technique 543
18.2 Special Issues 544
18.2.1 Shunt 544
18.2.2 Quality Check 544
18.2.3 Urgent Surgery 545
18.2.4 CEA/CABG: Staged, Combined, Reversed Approach 547
18.3 The Results of Surgery 548
18.3.1 Personal Experience 549
18.4 Endovascular Technique 549
18.4.1 Carotid Stenting Technique 549
18.4.2 Vascular Access 550
18.4.3 Diagnostic Catheters 550
18.4.4 Common Carotid Artery Access 550
18.4.5 Protection Systems 551
18.4.6 Stent Implantation 553
18.4.7 Pharmaceutical Protocol 554
18.4.8 Interdisciplinary Collaboration 556
18.4.9 Clinical Results of Carotid Stenting 556
18.4.10 Perioperative Complications 556
18.5 Conclusions 557
Biographies 562
References 558
Chapter 19: Drug Therapy and Follow-Up 564
19.1 Introduction 564
19.2 Physiopathology of Atherosclerosis as Target of Drug Action 567
19.2.1 Atherogenesis and Atherothrombosis 567
19.2.2 Endothelial Dysfunction 569
19.2.3 Lipoprotein Cholesterol Retention in the Arterial Intima 571
19.2.4 Proinflammatory Oxidized LDL and the Role of Monocytes–Macrophages 574
19.2.5 Apoptosis, Plaque Rupture, and Thrombus Formation 575
19.3 Biomarkers and Surrogate Endpoints 576
19.3.1 Quantitative Coronary Angiography 578
19.3.2 Carotid B-Mode Ultrasound 579
19.3.3 Coronary Intravascular Ultrasound 579
19.3.4 Magnetic Resonance Imaging 580
19.4 Hypolipidemic Drugs 581
19.4.1 Statins 581
19.4.1.1 Secondary Prevention Studies 583
19.4.1.2 Primary Prevention Studies 585
19.4.1.3 Angiographic Trials 585
19.4.1.4 Ultrasound Trials: cIMT Biomarkers 586
19.4.1.5 Coronary Intravascular Ultrasound Studies 586
19.4.1.6 Magnetic Resonance Imaging Studies 590
19.4.1.7 Pleiotropic Effects of Statins 591
19.4.2 Fibrates 594
19.4.3 Nicotinic Acid 597
19.4.4 Bile Acid Sequestrants 600
19.4.5 Cholesterol Absorption Inhibitors 601
19.5 Antihypertensive Drugs 603
19.5.1 Hypertension and Atherogenesis 603
19.5.2 The Renin-Angiotensin System as a Target of Antiatherosclerotic Drugs 605
19.5.3 First-Line Antihypertensive Drugs 608
19.5.4 Health Outcomes Associated with First-Line Antihypertensive Agents 610
19.5.5 Role of Blood Pressure Lowering 611
19.5.6 Antihypertensive Treatment and Carotid Intima–Media Thickness 614
19.6 Conclusions 617
References 617
Chapter 20: Control of Inflammation with Complement Control Agents to Prevent Atherosclerosis 633
20.1 Atherosclerosis 633
20.1.1 Pathogenesis of Atherosclerosis 633
20.1.2 Stages of Lesion Development 635
20.1.3 Animal Models of Atherosclerosis 635
20.1.4 Initiation and Progression of Atherosclerotic Lesions 636
20.1.5 Myocardial Infarction 637
20.1.6 Atherosclerotic Risk Factors 638
20.1.7 Low-Density Lipoprotein and Lipid Transport 639
20.1.8 Inflammation in Atherosclerosis 641
20.2 The Complement System 642
20.2.1 The Complement Cascade 642
20.2.2 Complement Activation Pathways 643
20.2.2.1 The Classical Pathway 643
20.2.2.2 The Lectin Pathway 645
20.2.2.3 The Alternative Pathway 645
20.2.2.4 The Membrane Attack Complex 646
20.2.3 Complement Inhibitors 646
20.2.4 The Complement Inhibitor Vaccinia Virus Complement Control Protein 647
20.2.5 Complement and Inflammation 647
20.2.6 The Complement System and Myocardial Infarction 648
20.3 The Role of Complement in Atherogenesis 648
20.3.1 Historical Notes 648
20.3.2 Complement and Cardiovascular Disease: Initial Findings 649
20.3.3 The Effect of VCP on Diet-Induced Atherosclerosis in C57BL Mice 651
20.3.4 Complement in Atherogenesis: Mode of Action 654
20.3.5 The Effect of Complement Inhibitors on Reperfusion Injury 656
20.3.6 Conclusions 659
Biographies 673
References 659
Part V Molecular and Emerging Technologies 676
Chapter 21: Vibro-Acoustography of Arteries 677
21.1 Introduction 677
21.2 Principle of Vibro-Acoustography 678
21.3 Detection of Arterial Calcifications: Experimental Results 679
21.4 Other Applications of This Technique 686
21.5 Detection Sensitivity 686
21.6 Image Resolution 687
21.7 Quantitative Measurements 687
21.8 Exposure Safety 688
21.9 Limitations of Vibro-Acoustography 688
21.10 Clinical Potential 689
21.11 Summary 690
Biographies 694
References 690
Chapter 22: Metabonomics in Patients with Atherosclerotic Artery Disease 697
22.1 Atherosclerosis and Metabonomics 698
22.2 Database and Subject Population Description 699
22.2.1 Patient Population 699
22.2.2 Instrumental Data 700
22.2.3 Hematochemical Variables 701
22.3 Analysis Architecture: Combination of ANOVA and Metabonomic Techniques 701
22.3.1 Correlation Analysis 703
22.3.2 Multidimensional ANOVA 704
22.3.3 Principal Component Analysis 704
22.3.4 Partial Least Squares 705
22.3.5 Discriminant Analysis 705
22.4 Database Reduction 706
22.5 Analysis of the Patients in Function of the Surgical Treatment 708
22.6 Patients and Plaque Type 711
22.7 Discussions and Future Perspectives 711
Biographies 716
References 713
Chapter 23: Molecular Imaging of Atherosclerosis 720
23.1 Introduction 721
23.2 Molecular Markers 721
23.3 Potential Molecular Targets of Atherosclerosis for Molecular Imaging 724
23.3.1 Adhesion Molecules 725
23.3.2 Oxidized LDL and Foam Cells 726
23.3.3 Neovessel Formation 726
23.3.4 Proteolytic Enzymes 727
23.3.5 Apoptosis 728
23.3.6 Fibrin Deposition and Thrombus Formation 728
23.4 Homing Ligands 729
23.5 Contrast Agents 731
23.6 Imaging Modalities 733
23.7 Image Analysis 736
23.8 Conclusions 738
Biographies 744
References 739
Chapter 24: Biologic Nanoparticles and Vascular Disease 745
24.1 Introduction 745
24.2 Infection and Atherosclerosis 746
24.3 History of Biologic Nanoparticles 746
24.4 Biochemical Characterization of Biologic Nanoparticles 747
24.5 Are Biologic Nanoparticles Lifeforms? 749
24.6 Biologic Nanoparticles as a Transmissible Cause of Disease 750
24.7 Nanoparticles: Toward a Unifying Hypothesis 753
24.8 Conclusions 753
Biographies 758
References 754
Chapter 25: (Shear) Strain Imaging Used in Noninvasive Detection of Vulnerable Plaques in the Carotid Arterial Wall 760
25.1 Introduction 761
25.2 Ultrasound Strain Imaging 762
25.3 Intravascular Strain Imaging 764
25.4 Noninvasive Strain Imaging Techniques 766
25.4.1 Longitudinal Cross-Section 767
25.4.1.1 Doppler-Based Methods 767
25.4.1.2 Registration-Based Method 767
25.4.1.3 Cross-Correlation-Based Methods 768
25.4.2 Transverse Cross-Sections 770
25.4.2.1 A-Line Based Beam Steering 770
25.4.2.2 Image-Based Beam Steering and Compounding 770
25.5 Noninvasive Shear Strain Imaging Techniques 772
25.5.1 Echo-Tracking 772
25.5.2 Relative Lateral Shift 773
25.5.3 Radiofrequency-Based Ultrasound 773
25.6 Conclusions 775
Biographies 779
References 775
Chapter 26: Intravascular Photoacoustic and Ultrasound Imaging: From Tissue Characterization to Molecular Imaging to Image-Guided Therapy 781
26.1 Intravascular Ultrasound and Photoacoustic Imaging 782
26.1.1 Intravascular Ultrasound Imaging 782
26.1.2 Intravascular Photoacoustic Imaging 783
26.2 Arterial Tissue Characterization Using Spectroscopic IVPA Imaging 785
26.3 Molecular and Cellular-Specific IVPA Imaging 789
26.3.1 IVPA Imaging of Macrophages Labeled With Au NPs: Cell Study 790
26.3.2 Spectroscopic IVPA Imaging of Macrophages in an Animal Model of Atherosclerosis 793
26.4 IVPA Monitoring of Stent Deployment 795
26.5 Design of an Integrated Catheter for Combined Coronary IVUS/IVPA Imaging 799
Biographies 808
References 804
Chapter 27: Evaluation Criteria of Carotid Artery Atherosclerosis: Noninvasive Multimodal Imaging and Molecular Imaging 811
27.1 Introduction 812
27.1.1 Clinical Symptoms of Carotid Artery Disease 813
27.1.1.1 Presurgery Evaluation 813
27.1.1.2 Postsurgery Evaluation 814
27.2 Presurgery Evaluation 814
27.2.1 Presurgery Evaluation by Imaging of Carotid Artery Disease 817
27.2.1.1 Available In Vivo Imaging Techniques 817
27.2.1.2 Choice of Imaging Modalities in Presurgery Evaluation 820
27.2.2 Plaque Classification and Plaque Typing 820
27.2.2.1 Human Atherosclerotic Lesions and ACC/ACR Classification on Imaging 820
27.2.2.2 A Proposed Carotid Artery Stenosis Evaluation of Plaque Characterization 824
Criteria of Patient Selection 826
Statistical Methods Used in Diagnostic Accuracy in In Vivo MRI Images 826
27.2.3 Presurgery Assessment of Carotid Plaque Magnetic Resonance Imaging and Spectroscopy In Vivo: Where We Are Today? 827
27.2.3.1 Magnetic Resonance Macroimaging at 1.5 T In Vivo of Carotid Arteries by Multiple Contrast 828
27.2.3.2 MRI at 1.5 T of Carotid Arteries In Vivo: Multiple Contrast Technique and Quantitative Analysis 829
27.2.3.3 Multiple Contrast Technique 829
27.2.4 Quantitative MRI Analysis 830
27.2.4.1 Segmentation4 830
27.2.4.2 Selection of TE and TR for Optimizing Contrast Between Specific Atheroma Core vs. Fibrous Cap Plaque Components 830
27.2.4.3 Parametric Imaging for Segmentation and Quantitation of Lesion Components Based on Their T1 and T2 Values 831
27.2.4.4 Feature Space Analysis for Segmentation and Quantitation of Different Lesion Components Based on Combinations of Their T1, T2, and PD Values 832
27.2.4.5 Boundary Detection 832
27.2.5 Time Series of Changes in Different Sets of Images from Same Location 833
27.2.6 Presurgery Evaluation of Aggressive Statin Treatment on Carotid Atherosclerotic Lesions by Serial Ultrasound and MRI Measurements 834
27.3 Postsurgery CEA 835
27.3.1 Selection Criteria of Surgical Procedure 835
27.3.2 Evaluation Criteria of Endarterectomy Specimen 836
27.3.2.1 Results 837
27.3.3 Plaque Histopathology Classification 839
27.3.4 Endarterectomy Procedure 839
27.3.5 Carotid Artery Tissue Processing 840
27.3.6 Development of a Technique for Diagnostic Accuracy and Measurement of Plaque Composition: MRM at 1.5 Tesla Ex Vivo 841
27.3.7 Carotid Plaque Magnetic Resonance Spectroscopy at 9.4 T Ex Vivo: Molecular Nature of Plaque Type III–IV in Excised Tissues 841
27.3.8 Discriminative Analysis of Plaque Constituents 843
27.3.9 Associations Between Histopathology and MRI: Diagnostic Accuracy and Quantitation of Plaque Features 844
27.4 Ex Vivo Molecular Staining Techniques in Atherosclerosis 845
27.4.1 Matrix Metalloproteases 845
27.4.2 DNA Microarray 846
27.4.3 The Protein Microarray 846
27.5 Multimodal Molecular Imaging of Atherosclerosis Plaque Activity: An Emerging Art 846
27.5.1 Multimodal Imaging Principles 848
27.5.2 Available Multimodal Imaging Techniques 850
27.5.3 Molecular Imaging of Carotid Artery Plaques: How it Works? 852
27.5.4 Present State of Art in Carotid Artery Atherosclerosis and Angiogenesis Imaging 854
27.5.5 3D Molecular Imaging of Biomarkers by Nanoparticles 855
27.5.6 MALDI Imaging Technique 856
27.5.7 Microfluidics in Carotid Artery Disease 859
27.5.8 3D Echographic Data Segmentation to Evaluate Carotid Artery Turbulence 860
27.6 Limitations of Techniques in Evaluation of CAD 860
27.7 Future of Molecular Imaging of Carotid Artery Disease and Nanotechnology 862
27.8 Conclusion 862
Biographies 870
References 862
Chapter 28: Ultrasound and MRI-Based Technique for Quantifying Hemodynamics in Human Cardiovascular Systems 872
28.1 Introduction 872
28.2 Ultrasound Doppler 873
28.2.1 Conventional Ultrasound Doppler 874
28.2.1.1 Continuous Wave Doppler 874
28.2.1.2 Pulsed Wave Doppler 876
28.2.2 Color Flow Mapping 879
28.2.3 Vector Doppler 881
28.3 Speckle Tracking 885
28.4 Transverse Oscillation 889
28.5 Echo Particle Image Velocimetry 892
28.6 Phase-Contrast MRI 898
28.6.1 Methodology 898
28.6.2 Flow Imaging Capabilities 900
28.6.2.1 Global Flow Parameters 900
28.6.2.2 Local Flow Parameters 902
28.6.3 Clinical and Research Applications 902
28.6.3.1 Recent Developments 903
28.6.3.2 Imaging Local Flow in the Carotid 904
28.7 Summary 905
Biographies 911
References 905
Editor Biographies 913
Index 916